The purpose of this grant is to support the CALGB Program in Correlative Sciences through support of the Correlative Sciences Committee Office at the Roswell Park Cancer Institute (RPCI) and the 10 Central Reference Laboratories or Facilities located at RPCI and 7 other Institutions. The primary objective of the proposed research is to evaluate the use of in vitro studies of the immunologic, cytogenetic and molecular genetic characteristics of leukemia, lymphoma and breast cancer cells to improve our ability to diagnose, classify, and treat these diseases in adults. The major specific aims of the current and proposed Correlative Sciences studies in leukemia are 1) to define the clinical significance of immunophenotype using multiparameter flow cytometry in adult AML and ALL, 2) to further define the clinical significance of chromosome analysis in adult AML, ALL, MDS, and CML, 3) to define the clinical and epidemiologic significance of RAS mutations in adult AML and MDS, 4) to define the incidence and clinical significance of loss of heterozygosity on chromosomes 5 and 7 in adult AML and MDS, 5) to further define the clinical significance of molecular analysis of the Philadelphia chromosome in ALL and CML, 6) to define the clinical significance of monitoring minimal residual disease (MRD) in adult ALL using an RNAse protection assay for tumor- specific rearrangements in T-cell receptor and immunoglobulin heavy chain genes, and 7) to develop a centralized tissue bank of tumor cells from patients with AML and ALL; in lymphoma, to determine 1) the clinical significance of monitoring MRD by PCR amplification of t(14;18) breakpoints in follicular small cleaved lymphoma, and 2) the clinical significance of monitoring MRD by RNAse protection assay for rearranged antigen receptor genes in intermediate grade lymphoma; in breast cancer (BrCa) to determine 1) the clinical significance of ploidy and S-phase activity in stage II BrCa, 2) the role of erb B2, p53, and cathepsin D overexpression, determined immunohistochemically, as prognostic and therapeutic markers, 3) the clinical significance of genetic abnormalities (amplification of HER-2 gene or the INT-2 locus, mutations in p53) in stage II BrCa, 4) the prognostic significance of staining of primary BrCa tissue with a monoclonal antibody to the core protein of DF3 mucin-like antigen, 5) by immunohistochemical study the prognostic significance in BrCa of expression of nm23 anti-metastatic marker, MMP-2, TIMP-2, and PCNA, 6) the prognostic significance of neo- angiogenesis in stage II primary BrCa tissue determined by staining for factor VIII, and 7) if elevated circulating or urinary levels of bFGF angiogenic factor predict clinical course in BrCa. These specific aims will be accomplished through 12 ongoing and 3 closed CALGB Studies, as well as 4 under development. The Correlative Sciences Committee is chaired by Clara D. Bloomfield, M.D. (RPCI). The Program is developed, coordinated, and administered through the Correlative Sciences Committee Offices at RPCI. The proposed research should increase our understanding of the biology, diagnosis, classification, and treatment of adults with leukemia, lymphoma, and BrCa.